In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity.